The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]


Variant: NM_000260.4(MYO7A):c.2527G>A (p.Val843Met)

CA132253

43185 (ClinVar)

Gene: MYO7A
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
UUID: 70b30bc6-7744-4a79-848e-530d07e58aa7
Approved on: 2022-08-03
Published on: 2022-08-03

HGVS expressions

NM_000260.4:c.2527G>A
NM_000260.4(MYO7A):c.2527G>A
NM_000260.4(MYO7A):c.2527G>A (p.Val843Met)
NC_000011.10:g.77179894G>A
CM000673.2:g.77179894G>A
NC_000011.9:g.76890940G>A
CM000673.1:g.76890940G>A
NC_000011.8:g.76568588G>A
NG_009086.1:g.56631G>A
NG_009086.2:g.56649G>A
ENST00000409709.9:c.2527G>A
ENST00000409893.6:n.592G>A
ENST00000670577.1:n.368G>A
ENST00000409619.6:c.2494G>A
ENST00000409709.7:c.2527G>A
ENST00000409893.5:c.2527G>A
ENST00000458169.2:n.70G>A
ENST00000458637.6:c.2527G>A
ENST00000481328.7:n.70G>A
ENST00000620575.4:c.2527G>A
NM_000260.3:c.2527G>A
NM_001127179.2:c.2527G>A
NM_001127180.1:c.2527G>A
NM_001127180.2:c.2527G>A
NM_001369365.1:c.2494G>A
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Uncertain Significance

The Expert Panel has overridden the computationally generated classification - "[unknown]"
Not Met criteria codes 5
BP4 BP2 PP3 PM3 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.2527G>A variant in MYO7A is a missense variant predicted to cause substitution of valine by methionine at amino acid 843. The variant is present in 0.0006965 (23/22568) of South Asian alleles with a confidence interval of 95% in gnomAD v2.1.1. The computational predictor REVEL gives a score of 0.25, which is neither above nor below the thresholds predicting a damaging or benign impact on MYO7A function. The variant has been reported in 6 probands, all of whom did not have clinical/phenotypic data, had other potentially pathogenic variants, or did not present with hearing loss (PMID:30755392, GeneDx, EGL Eurofins, Illumina). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive Usher syndrome based on the absence of ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP (ClinGen Hearing Loss VCEP specifications version 2; 7/20/2022).
Not Met criteria codes
BP4
The computational predictor REVEL gives a score of 0.25, which is neither above nor below the thresholds predicting a damaging or benign impact on MYO7A function.
BP2
Phasing information unknown after contacting GeneDX about patient with pathogenic variants in GJB2.
PP3
The computational predictor REVEL gives a score of 0.25, which is neither above nor below the thresholds predicting a damaging or benign impact on MYO7A function.
PM3
Gene Dx internal data: "We’ve observed this variant in 2 patients, both of whom were reported with only hearing loss: 1 patient was only a carrier for another pathogenic variant in a recessive gene, no other potentially causative variants observed. 1 patient harbored causative pathogenic variants in GJB2 and GJB6 (the common deletion), as well as variants of uncertain significance in 2 other genes. EGL Eurofins internal data: "We’ve detected the MYO7A variant heterozygous on 1 hearing loss panel. It was the only reported variant, and we had no clinical information on this individual." Illumina internal data: "The MYO7A c.2527G>A (p.Val843Met) variant was detected as part of our TruGenomeTM Predisposition Screen test, this time in two unrelated individuals...we do not have any phenotypic details but as far as we know, the individuals carrying these variants have no known phenotype." From Ji (2019) Cold Spring Harb Mol Case Stud 5: PubMed: 30755392: One individual reported with multisystemic phenotypes, none of which include hearing loss. The variant has been reported in 6 probands, all of whom did not have clinical/phenotypic data, had other potentially pathogenic variants, or did not present with hearing loss (PMID:30755392, GeneDx, EGL Eurofins, Illumina).
BS1
The variant is present in 0.0006965 (23/22568) of South Asian alleles with a confidence interval of 95% in gnomAD v2.1.1.
Curation History
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